Papillomavirus: Viral vectors in the gene therapy and new therapeutic targets

Abstract

Epitheliotropic and mucosotropic Papillomaviruses (PVs) constitute the Papillomaviridae family. There are 26 genera comprising levels of inter species genetic similarities by nucleotide sequence analysis of the L1 viral region, the generally most conserved region among papillomaviruses. There is an increasing consensus that the ideal vector for gene therapy should be completely based on chromosomal elements and behave as an independent functional unit after integration. The present paper is a short review about epidemiology of HPV infection, vaccines anti-HPV and tumors associated with HPV and gene therapy including biological vectors, stem cells, viral and non-viral vectors and chromosome-based vectors. Furthermore, new therapeutic targets and vectors applied in gene therapy of other viruses are some of the examples that have been successfully modified by recombinant DNA techniques. New biotechnologies in molecular biology have been applied in papillomavirus research and are still being investigated for the application in the gene therapy. RNA-sequencing (RNA-seq) for analysis of the transcriptome, multiply-primed rolling circle amplification (RCA) used to identify novel human papillomaviruses (HPV) and new DNA sequencing method based on real-time phyrophosphate are examples as new techniques.

mRNA vaccines in cancer clinical trials: HPV16 tumor-derived antigens (e6 and e7 oncoproteins) associated with head and neck squamous cell carcinoma (HNSCC), oropharyngeal and cervical cancers

“…DNA-based vaccines, recombinant proteins, nanoparticles, synthetic peptides, viral and non-viral vectors may be novel therapeutic targets to HPV vaccination [7]. So, mRNA vaccines encoding tumor-associated antigens (TAA) as CEA (Carcinoembryonic Antigen), HER2/neu, MUC1 (Mucin 1), NY-ESO-1 associated colorectal and other adenocarcinomas, gastric cancer, colorectal cancer, epithelial cancers, esophageal cancer, respectively [5].…”

Next generation of mRNA and lncRNAs based-vaccines platforms: Highlighted for HPV in head and neck squamous cell carcinoma, cervical and colorectal cancers and oncogenic viruses HBV/HCV in hepatocellular carcinoma

“…Experimental studies in mice and non-human primates showed strong immunogenicity and anti-tumor effects demonstrating messenger RNA-HPV therapeutic vaccine as prophylactic vaccine for HPV [8]. Therefore, another platforms DNA-based vaccines, recombinant proteins, nanoparticles, synthetic peptides, viral and non-viral vectors may be novel therapeutic targets and prophylactic HPV vaccination [12] (figure 1).…”

Prevalence of High-Risk Human papillomavirus Genotypes and Predictors factors for Cervical Cancer in Unimmunized Brazilian Women without Cytological Abnormalities

“…The mucosal HPV types have been described in the Alpha papillomavirus genus that infects the anogenital epithelium. HPV is the most common sexually transmitted disease based on their oncogenic activity as high-risk (hr) type, low-risk type (lr) and type of undeterminedrisk depending upon the associated diseases [1][2][3].…”